Rapid Immunodiagnosis of Drug-Resistant Bacterial Pathogens

耐药细菌病原体的快速免疫诊断

• 批准号: 8699863
• 负责人: MARK GEISBERG
• 金额: $ 30万
• 依托单位: SILVER LAKE RESEARCH CORPORATION
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-10 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8699863
• 关键词: Address; Affinity; Antibiotics; Antibodies; Area; Bacterial Antibiotic Resistance; Bacterial Infections; Binding; Bioinformatics; California; Clinical; Collaborations; Collection; Detection; Development; Diagnostic; Diagnostic tests; Drug resistance; Effectiveness; Enzyme-Linked Immunosorbent Assay; Enzymes; Epitopes; Fluoroquinolones; Generations; Home environment; Immunization; Immunoassay; Immunological Diagnosis; Infection; Institution; Laboratories; Lactamase; Lactams; Lateral; Legal patent; Medical; Methodology; Methods; Microbiology; Monobactams; Monoclonal Antibodies; National Institute of Allergy and Infectious Disease; Patients; Peptides; Pharmaceutical Preparations; Phase; Phenotype; Pregnancy Tests; Production; Proteins; Public Health Schools; Recombinants; Recording of previous events; Reliance; Reporting; Research; Resistance; Sampling; Silver; Source; System; Testing; Universities; Urinary tract infection; Urine; Uropathogen; Ursidae Family; Western Blotting; bacterial resistance; clinical practice; pathogen; prevent; public health relevance; screening; trait

DESCRIPTION (provided by applicant): Bacterial resistance to ¿-lactam antibiotics is threatening to limit the effectiveness of this most- used class of antibiotics. A major contributin factor to this problem is the lack of rapid testing methods for medical practitioners to identify ¿ lactam-resistant pathogens before prescribing specific antibiotics. For urinary tract infections (UTIs), the most common bacterial infections in the world, older ¿-lactam antibiotics are not used despite the fact that >60% of uropathogens are sensitive to these drugs. Resistance to ¿-lactam antibiotics is conferred by the expression of ¿-lactamases, enzymes that deactivate the antibiotics. We propose the development of a rapid immunoassay test kit for detection of any of a wide range of ¿-lactamases. In Phase I of this project, we aim to develop cross-reactive monoclonal antibodies (MAbs) targeting the homologous regions of the most clinically problematic classes of ¿-lactamases - extended- spectrum -lactamases (ESBLs) and carbapenemases - and then to develop a sandwich ELISA capable of distinguishing -lactam-resistant clinical bacterial isolates from ¿-lactam-sensitive isolates. In Phase II, we will aim to convert this laboratory ELISA into a robust, 10-minute lateral flow immunoassay test kit (similar to the home pregnancy test), capable of detecting ¿-lactamases, and therefore ¿-lactam resistance, directly in patient samples. This capability promises to revolutionize current clinical practice for treatment of (UTIs), allowing the effective use of even the earliest ¿-lactams and preventing the selection of resistance to current first-line treatments.

描述（由申请人提供）：细菌对β-内酰胺抗生素的耐药性有可能限制这类最常用抗生素的有效性。造成这个问题的一个主要因素是缺乏可供医生识别的快速检测方法 ¿ 在开具特定抗生素之前先检查内酰胺耐药病原体。对于尿路感染 (UTI) 这种世界上最常见的细菌感染，尽管超过 60% 的尿路病原体对这些药物敏感，但并未使用较旧的β-内酰胺抗生素。对β-内酰胺抗生素的耐药性是由β-内酰胺酶（使抗生素失活的酶）的表达赋予的。我们建议开发一种快速免疫检测试剂盒，用于检测各种β-内酰胺酶。在该项目的第一阶段，我们的目标是开发针对临床上最有问题的β-内酰胺酶 - 超广谱内酰胺酶（ESBL）和碳青霉烯酶类别的同源区域的交叉反应性单克隆抗体（MAb），然后开发能够区分β-内酰胺耐药的临床细菌分离株的夹心ELISA ¿-内酰胺敏感分离株。在第二阶段，我们的目标是 将此实验室 ELISA 转换为强大的 10 分钟侧流免疫测定试剂盒（类似于家庭妊娠测试），能够直接检测患者样本中的 β-内酰胺酶，从而检测 β-内酰胺耐药性。这种能力有望彻底改变当前的临床 尿路感染（UTI）治疗实践，允许有效使用甚至最早的β-内酰胺，并防止对当前一线治疗产生耐药性。